posted on 2021-10-19, 19:08authored byYing Li, Honglin Wen, Xizhen Ge
Berberine (BBR) is an effective drug
for human intestinal inflammation
by preventing intestinal adhesion of bacterial pathogens, while its
antibacterial activity is ineffective. Although the antimicrobial
mechanisms of BBR are intensively studied at high concentrations,
the response of pathogens to its low concentrations remains poorly
understood. Here we demonstrated that low concentrations of BBR (3
and 6 μg/mL) conferred by hormesis accelerated cell growth of
an important Gram-negative pathogen, Klebsiella pneumoniae, in vitro, while higher concentrations (25 and
50 μg/mL) resulted in the opposite. Transcriptome analysis of K. pneumoniae revealed the up-regulated expression of the
KmrA efflux pump and further confirmed it was hypersensitive to BBR
stress. Strikingly, when cultivated in tetracycline, the growth-promoting
effect of BBR became more significant, while this effect was reversed
in the presence of the efflux pump inhibitor cyanide-m-chlorophenylhydrazone. The hormesis was also found in Enterobacter
cloacae and Acinetobacter baumannii. More
importantly, the presence of BBR at low concentrations resulted in
higher minimal inhibitory concentrations of efflux-related antibiotics
such as rifampicin and azithromycin. Overall, our data demonstrated
the hormesis of BBR and revealed the potential risk of its applications
against Gram-negative pathogens at low concentrations.